Lorenza Rimassa is Associate Professor of Medical Oncology at Humanitas University, Pieve Emanuele, Milan (Italy), and Head of the Autonomous Hepatobiliopancreatic Oncology Section at the IRCCS Humanitas Research Hospital in Rozzano, Milan (Italy). An internationally recognised specialist in the treatment of liver, pancreatic and biliary tract cancers, she is actively involved in numerous clinical trials and translational research activities. In this interview, conducted at the ESMO GI 2025 congress in Barcelona, Professor Rimassa guides us through the most significant developments that emerged from the congress and reflects on the present and future of hepatobiliary and pancreatic oncology.
esanum: A few weeks ago, the ESMO GI 2025 congress was held in Barcelona. Which studies related to your field of research sparked your interest the most?
Prof. Rimassa: Once again this year, the ESMO Gastrointestinal Cancers Congress was a significant occasion for our community. Although the studies presented in the field of locally advanced pancreatic cancer, hepatocellular carcinoma and biliary tract tumours did not reveal any groundbreaking news, we did receive confirmation of data that has the potential to bring about concrete changes in our future clinical practice.
Among the most significant contributions are the results of the phase III PANOVA-3 study, which evaluated the addition of alternating electric field therapy (TTFields) to the combination of gemcitabine and nab-paclitaxel in patients with locally advanced and unresectable pancreatic cancer. This is a non-pharmacological approach that, for the first time in this setting, has demonstrated a benefit in terms of overall survival and, above all, better pain control, with a prolongation of the symptom-free period and reduced use of opioids. In such a difficult context, where treatment options are limited and the burden of symptoms is often heavy, these results represent an important clinical innovation. Quality of life, often overlooked in trials, has become a central parameter for evaluating efficacy.
With regard to hepatocellular carcinoma, two studies deserve particular attention. The first is the phase III TALENTACE study, which demonstrated that in Asian patients with liver-limited hepatocellular carcinoma, the combination of locoregional therapy (TACE) and systemic therapy with atezolizumab + bevacizumab prolongs progression-free survival compared to TACE alone.
This is an Asian study, but two previous global phase III studies, EMERALD-1 and LEAP-012, had already demonstrated the advantage of combining TACE and different immunotherapy regimens, and we expect this approach to enter clinical practice soon. The quality of life analysis from the phase III CheckMate 9DW study was also presented, showing that the combination of nivolumab and ipilimumab is not only more effective than tyrosine kinase inhibitor therapies (lenvatinib or sorafenib) in the first line, but is also associated with a longer maintenance of good quality of life.
In parallel, the SIERRA study, a phase IIIb trial, evaluated the STRIDE immunotherapy combination (tremelimumab + durvalumab) in a particularly fragile population: patients with unresectable hepatocellular carcinoma and unfavourable clinical conditions, such as suboptimal liver function (Child-Pugh B7/B8), ECOG performance status 2 or vascular invasion Vp4.
The combination was confirmed to be manageable in terms of safety, with an incidence of 19.4% of grade 3-4 treatment-related adverse events and 32.7% of serious adverse events. In particular, no unexpected safety concerns emerged in the safety analysis, despite the worse risk profile compared to that of the population in the phase III HIMALAYA study, from which the approval of the STRIDE regimen itself derives.
To better understand the value of these findings, it is also useful to refer to the long-term data from the HIMALAYA study, published in 2025 in the Journal of Hepatology. In this phase III study, conducted in patients with unresectable HCC, in good general condition and with preserved liver function, the STRIDE combination showed a 5-year overall survival rate of 19.6%, compared to 9.4% with sorafenib. The effect on survival was consistent across all subgroups analysed, and no new signs of late toxicity emerged.
Together, these two studies provide an increasingly robust picture of STRIDE's potential in the management of HCC, both in selected patients and in those at higher risk, opening up new therapeutic possibilities even in the most challenging clinical settings.
Another rapidly evolving area is that of bile duct tumours. Precision medicine is finally finding practical application in this group of rare and aggressive neoplasms. The phase IIIb ProvIDHe study, conducted in a real-world setting, confirmed the efficacy of ivosidenib in patients with IDH1-mutated cholangiocarcinoma who had already been pretreated with medical therapy, reporting disease control and survival rates similar to those observed in the phase III ClarIDHy study. Again, the added value is not only the efficacy of the drug, but the confirmation that this efficacy is maintained even outside selected contexts. Furthermore, the crucial role of correct molecular profiling, which is essential for targeted drug therapy, is confirmed.
Finally, another study presented in an oral session evaluated the use of olaparib in patients with advanced biliary tract tumours who carry mutations in homologous recombination genes, such as BRCA1/2 and PALB2. Despite the heterogeneity of the population, the results showed a good disease control rate and promising overall survival, with no unexpected toxicity profiles. Again, the challenge is not only therapeutic but also organisational: to make access to these targeted therapies possible, it is essential to ensure timely and widespread molecular diagnostics.
The overall impression is that research is finally responding to the real needs of our patients. Trials are not just about numbers or hazard ratios, but increasingly focus on what matters in everyday life: symptom control, quality of life, and treatment tolerability. This is a direction we must continue to pursue with determination.
esanum: In recent years, we have witnessed a significant evolution in the management of biliary tract tumours. What do you think are the key points today for truly improving the care of these patients?
Prof. Rimassa: I believe that the real revolution in the management of biliary tract tumours has not only taken place on a pharmacological level, but, even more so, on a cultural and organisational level. If we look at the last 6-7 years, we have taken a decisive step forward in understanding the biology of these tumours, which have always been characterised by molecular heterogeneity, rarity and late diagnosis. This greater knowledge has opened up new perspectives, but it has also required a profound revision of the treatment pathway.
Today, we know that every patient with a bile duct tumour should undergo complete molecular profiling as soon as possible. This step, which may seem technical, is actually fundamental: it allows us to identify target alterations such as IDH1, FGFR2 or HER2, which pave the way for targeted therapies already available in Italy or in advanced stages of clinical development. However, for profiling to be useful, it must be integrated from the first line of treatment.
For this reason, it is crucial to start with standard chemo-immunotherapy, such as the combination of gemcitabine/cisplatin, combined with an immunotherapy agent such as durvalumab, based on data from the TOPAZ-1 study, or pembrolizumab, as per the KEYNOTE-966 study, while molecular analyses are carried out in parallel.
In recent years, knowledge of the biology of bile duct tumours has improved significantly. However, this increased awareness loses its effectiveness if the healthcare system is not ready to transform it into real opportunities for patients. For example, early molecular profiling is needed, to be performed within the first line of treatment, to identify target genetic alterations such as IDH1, FGFR2 or HER2. These biomarkers guide subsequent therapeutic choices: ivosidenib in IDH1-mutated cholangiocarcinoma, pemigatinib/futibatinib for FGFR2 fusions or zanidatamab in HER2-positive cases.
To be meaningful, every therapeutic advance must be accessible.
esanum: What are the main obstacles preventing equitable access to new diagnostic and therapeutic strategies for liver, pancreatic and biliary tract cancers?
Prof. Rimassa: One of the key issues that has emerged in recent years is that access to diagnostic technology and innovative therapies is no longer optional: it is a clinical imperative.
Alongside scientific progress, systemic change is needed: cancer patients must be treated immediately in referral centres, where oncologists, hepatologists, surgeons, radiologists, radiotherapists, pathologists and molecular biologists work together. It is true multidisciplinarity, not just declared multidisciplinarity, that makes the difference. And it is only thanks to a structured network that we can guarantee rapid diagnosis, access to tests and, above all, access to innovative treatments.
It is not enough to know that a molecule is active in a specific subgroup if the patient is not tested or if the drug is not available nationally or regionally. For this reason, we must work not only as clinicians but also as a system, so that precision medicine does not remain an opportunity for the few but becomes an integral part of the routine management of rare oncological diseases such as bile duct cancer.
Two recent publications in The Lancet Regional Health - Europe highlight how there are significant disparities in Europe in access to diagnostics and targeted therapies, with critical issues accentuated in economically disadvantaged countries. This includes not only insufficient laboratories but also a lack of multidisciplinary teams and delays in diagnostic pathways.
Scientific research is advancing, but without an orderly system to translate these discoveries into real availability (rapidly available molecular tests, access to drugs in the short time following first-line treatment, facilities capable of operating in an integrated manner), the impact of progress remains partial. The priority today is to reduce regional inequalities, establish standardised clinical guidelines and incentives for the full development of precision medicine, even for the rarest cancers.
esanum: What concrete actions can therefore be taken to improve access to medical innovations in the field of oncology, especially for hepatobiliary and pancreatic cancers?
Prof. Rimassa: Ensuring access to innovation does not just mean having new drugs or diagnostic tests available: it means putting every patient in a position to truly benefit from them. It is a cultural shift, even more than a clinical one. This is especially true in rare and complex cancers such as those of the bile ducts, liver or pancreas, where time is often short and precision medicine can play a crucial role.
Where economic resources are lacking, those responsible for administering public health need to make expertise, facilities and drugs available to the community. Even if these elements are present, they are not sufficient to guarantee full access to innovative methods if there is no system or network to connect the resources.
We cannot expect an oncologist in a peripheral centre, who deals with all types of cancer, to be up to date on the latest developments in low-incidence cancers. However, there needs to be a simple protocol that allows them to identify situations that require consultation with a reference centre.
One of the most concrete actions we have implemented, for example in Lombardy, has been the establishment of a regional working group dedicated to molecular profiling in biliary tract tumours. This project, developed in collaboration with Regione Lombardia (the governing authority of Lombardy, a region in northern Italy), involved centres of excellence and hospitals in the area in a hub & spoke network, which allows tests to be centralised in the most experienced laboratories while ensuring that all patients, even those treated in peripheral facilities, have access to advanced molecular diagnosis within a reasonable time frame. It is a replicable model that combines efficiency, equity and quality.
A truly multidisciplinary organisation is needed, in which oncologists, hepatologists, surgeons, radiologists, radiotherapists, pathologists and molecular biologists work together from the moment of diagnosis. Above all, a network of collaboration is needed between the healthcare system and patient associations, which are increasingly playing a leading role in guiding treatment priorities and advocacy.
In this context, Italy has valuable organisations such as APiC (Italian association for patients with cholangiocarcinoma), dedicated to patients with cholangiocarcinoma, and clinical initiatives such as IRaBiCa (The Italian Rare Biliary tract Cancer initiative), which bring together professionals and patients to improve access to studies and genetic testing. At European level, organisations such as AMMF - The Cholangiocarcinoma Charity in the United Kingdom and Digestive Cancers Europe offer information tools, emotional support and links to research.
esanum: What role can artificial intelligence play in oncology, particularly in the diagnosis and therapeutic management of hepatobiliary and pancreatic tumours?
Prof. Rimassa: Artificial intelligence is gradually entering clinical oncology practice, and I believe its potential is truly remarkable, especially in complex areas with high biological heterogeneity such as liver, biliary tract and pancreatic tumours.
We are already beginning to see promising applications. For example, in hepatocellular carcinoma, predictive algorithms are being developed that, by integrating clinical, laboratory and radiological data, can flag suspicious changes early on, even before they become evident on traditional imaging. This could revolutionise surveillance approaches in cirrhotic patients, improving early diagnosis and therefore prognosis. In addition, recent studies have shown that it is possible to combine deep learning algorithms with the analysis of immunohistochemical markers to predict response to systemic treatments, as in the case of the atezolizumab-bevacizumab combination.
Even in biliary tract tumours, which are rare and difficult to classify, artificial intelligence can help us build models capable of better stratifying risk, selecting patients eligible for targeted therapies and optimising the sequence of treatments.
Clearly, we are still in the early stages: in order to use these tools reliably, we need prospective validation, integration with clinical networks and constant dialogue between those who treat patients and those who develop technology. But I have no doubt that AI will become an integral part of our daily work in the future, supporting us in increasingly complex decisions, especially in contexts where every detail can make a difference.
esanum: What message would you give to young researchers or clinical oncologists who have just started their professional careers?
Prof. Rimassa: The incidence of cancer is constantly increasing, affecting even younger segments of the population - this is a phenomenon whose causes we do not yet fully understand. So, although medicine today has scientific and technological knowledge that enables it to progress at a pace that was unthinkable a few decades ago, the challenges to be faced are numerous and complex, not only to enable the recovery of most patients, but also to enable an ever-better quality of life, even during the course of the disease.
I would advise young people entering this profession to focus their efforts on early diagnosis. This is the area where we can really make a difference, the area that can powerfully change patients' clinical history. In oncology, of course, everything deserves attention and development, such as primary prevention and the search for effective therapies. However, I believe that achieving early diagnosis of tumours that we currently only discover at an advanced stage, or predicting an individual's likelihood of developing the disease or responding effectively to therapy, would be a milestone in oncology.